A snapshot of success

A self-described 'specialised zoologist,' Laureate Professor Roger Smith is keen on understanding the idiosyncrasies, interactions and inner workings of multiple animal species but especially human.

Laureate Professor Roger Smith is a man of many talents and interests. As the Co-Director of the University of Newcastle's Priority Research Centre for Reproductive Science, and the Director of the University's Mothers and Babies Research Centre and the Department of Endocrinology at John Hunter Hospital, he's also a man with many responsibilities. Not limiting himself to a singular field, the passionate academic freely studies "anything and everything" that sparks his intrigue.

"I don't' have a single focus," Roger elaborates.

"To give you an idea, I have about 25 different projects going at the moment."

"These range from explorations of potential new treatments for women in premature labour and women with postpartum haemorrhage, to the use of nanoparticles to treat thyroid and ovarian cancers."

"I'm very lucky to be able to do what I do."

A head start

Roger recalls having this affinity for the natural world from a young age. Working on the proviso that the "proof is in the picture," the esteemed educator tells of a photograph of his toddler-self feeding elephants, and its importance in kick starting his research career.

"I was thinking about how the planet works very early on in my life," he reflects.

Seeking to satisfy this time-honoured thirst for knowledge about his own species, Roger studied medicine at the University of Sydney. Graduating in 1973, he spent the next two years at Royal North Shore Hospital followed by time in Western Australia and New Zealand, before undertaking a PhD at the University of London.

"I saw my training to become a doctor as training to become a specialised zoologist," he explains.

"My interest in people is not just in terms of their diseases, but also about how they interact with each other."

"We are the most highly social animal there is."

"This is the way I see myself and what I can contribute to our society."

After completing his doctorate in 1981, Roger returned to Australia and joined the University of Newcastle.

Well-known and well-travelled

Most recently, and perhaps most interestingly, Roger has been undertaking a research assignment on lemurs in Madagascar.

"They are surprising and extremely complex primates," he describes.

"The females are dominant over the males and their clitorises are bigger than penises, due to the different steroids produced during pregnancy."

"Oestrogen and progesterone normally regulate the onset of labour but they do all of these crazy things in lemurs so we don't yet know why they give birth when they do."

"People from the island's west coast have collected samples of poo from pregnant female lemurs and they've been transported here for analysis and comparison with samples obtained from Taronga Western Plains Zoo in Dubbo."

Spanning a generous handful of time zones, Roger's current work also sees him conducting work in Nepal. The clinical endocrinologist is on the hunt for ways to improve maternal mortality in the developing country, ambitiously and admirably looking to reduce its "exceedingly high" death rates during pregnancy.

"Women are of low standing in this culture," he points out.

Collaborating with a Nepalese postgraduate student, Roger is hoping to change this situation with a simple but powerful song.

"Music is a big part of day-to-day community life for these people," he illuminates.

"So we're going to run a competition in schools for a lyrical number that involves some key messages about respecting women."

"It will be judged by teachers – who are all male."

"Once the final song is chosen, it will be taught to travelling minstrels who will then sing it at every house in the intervention area."

"We will assess the impact of the song on attitudes to pregnant women and the care they need."

In our own backyard

Back home, Roger is endeavouring to 'close the gap' where Aboriginal health is concerned. He has set up programs in both Tamworth and Walgett, renting and renovating buildings for art and ante-natal research purposes.

"Indigenous women have double the rate of premature birth and double the rate of growth retarded babies," the multitasking scholar affirms.

"But we're trying to improve those statistics."

"We've employed Aboriginal artists and elders, as well as dieticians, midwives and lactation consultants to pass on their knowledge to expectant mothers."

"Together, they all sit down and do artworks and discuss their different areas of expertise."

Learning just as much from these women as he is by teaching them, Roger asserts the rural venture has so far been an "overwhelming success."

Thinking outside the norm

When asked where he would like to see the future of medicine and public health, Roger is quick to answer.

"They both need to change," he claims.

"These days, the troubling and most prevalent diseases are social problems – not medical ones."

"So I could tell you to eat less, start exercising and stop smoking, but then you go back to your world surrounded by family and friends who probably drink more than they should, smoke and don't exercise often."

"My five minutes with you is a waste of time."

Believing how we behave and think is "largely determined" by the people around us, Roger is calling for doctors to influence the social networks of individuals.

"I no longer meet with patients one-on-one," he reveals.

"If someone has obesity or smokes, for example, I want to meet their partner and friends and relatives."

"It's about group effort."

"After all, you can't refuse to help someone you love and care about."

Career Summary

Biography

I am an internationally recognised leader in the pathophysiology of human pregnancy. I have been awarded medals and published in Nature, Nature Medicine and the New England Journal of Medicine and Scientific American; Science has reviewed my work. I have been a visiting Professor at Harvard, Yale and the NIH Perinatal Research Branch.

Research ExpertiseClinical and basic science expertise in the physiology of human birth and the pathophysiology of premature birth.

Teaching ExpertiseTeaching endocrinology to medical students

Administrative ExpertisePrevious assistant dean research, currently Director of the Department of Endocrinology John Hunter Hospital and Co-Director of the University of Newcastle Priority Research Centre in Reproductive Science and Director of the Mothers and Babies Research Centre.

Qualifications

PhD, University of London

Bachelor of Medicine & Surgery, University of Sydney

Keywords

endocrinology

premature labour

preterm birth

Fields of Research

Code

Description

Percentage

110399

Clinical Sciences not elsewhere classified

35

111499

Paediatrics and Reproductive Medicine not elsewhere classified

50

060499

Genetics not elsewhere classified

15

Professional Experience

UON Appointment

Title

Organisation / Department

Professor

University of NewcastleSchool of Medicine and Public HealthAustralia

Professor

Priority Research Centre (PRC) for Healthy Lungs | The University of NewcastleSchool of Medicine and Public HealthAustralia

Professor

University of NewcastleSchool of Medicine and Public HealthAustralia

Awards

Distinction

Year

Award

2014

Fellow of the Australian Society of Reproductive BiologyAustralian Society of Reproductive Biology

2012

Life Member Endocrine Society of Australia for services rendered Endocrine Society of Australia

Fellowship ad eundemThe Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG)

2000

Asia & Oceania MedalSociety for Endocrinology

2000

Award for Research ExcellenceHunter Medical Research Institute (HMRI)

Invitations

Participant

Year

Title / Rationale

2005

1st International Summit on Preterm BirthOrganisation: Society for Gynaecological Investigation
Description:
Roger was invited to give a Plenary lecture "Stress and the onset of human labour" in the session called "Preterm labour - mechanisms". This was the first in a series of landmark meetings focussed on topics vital to global reproductive health. This Summit addressed the important research questions relating to the prediction and prevention of preterm birth. The goal of the Summit was to produce an expert consensus document defining the current state of knowledge and important questions to be addressed in future research. Roger was also invited to be on the Scientific Committee of the Summit. This report and supporting documents were published in the Journal of the Society of Gynecological Reproduction.

2004

2nd International workshop on Biomarkers and PTDOrganisation: World Health Organisation
Description:
Roger was one of two Australian participants. The goals for this workshop were to generate a forum for international projects, future collaborations scientific progress based on fruitful discussions, exchange of ideas and potentially friendship. The final product was to be scientific protocols owned by all participants. 5 protocols on genetics, preconception identification of women at risk for PTB, Pathways, Time trends and preventions and interventions were generated. The International PREterm BIrth Collaborative (PREBIC) was formed at this meeting.

2003

46th RCOG Study GroupOrganisation: Royal College of Obstetrics and Gynecology
Description:
Invited to participate in the 46th Royal College Obstetrics & Gynecology Study Group on preterm labour convened in London 21-23 Oct 2003 A small number of selected people were chosen to meet for three days to discuss preterm labour. The college attaches great importance to the Study groups both nationally and internationally through the resulting publication. Roger's talk was titled Control of the length of gestation lessons from women". This led to the following publication. Smith R, Mesiano S, Nicholson R, Zakar T, Chan E-C, Bisits A, Clifton V, Giles W. Control of the Length of Gestation-Lessons from Women. Pre-term Birth Study Group. Eds. Bennet and Thornton. Publisher: Royal College Obstetrics Gynecology 2004.

Preterm birth accounts for 70% of neonatal mortality and is a common cause for intellectual handicap among survivors. Approximately 50% of cases of cerebral palsy are associated w... [more]

Preterm birth accounts for 70% of neonatal mortality and is a common cause for intellectual handicap among survivors. Approximately 50% of cases of cerebral palsy are associated with preterm birth, in turn preterm birth increases the risk of cerebral palsy by 40 times! (Goldenberg, 2002). Preterm labor thus afflicts individuals at the very beginning of their lives, depriving them of opportunities and increasing health and educational costs for families and society in general. Unfortunately the rates of preterm birth have not changed for over 30 years due to an inability to predict the event and lack of effective therapies. This clinical problem has driven research into the mechanisms that regulate the timing of human birth and the disorders which cause preterm birth. For reasons of ethics most research in the past has focused on animal work, especially in the sheep. Unfortunately studies have revealed substantial differences between parturition in humans and that in other animals. Thus animal studies provide us with clues as to how systems operate to regulate delivery in mammals but frustrate us with uncertainty as to whether particular mechanisms operate in the human. Experimental in vivo studies provide the strongest evidence for cause and effect, yet the closer we come to the human state in our near relatives the apes, the larger the ethical constraints on experimental studies become.

Background: In 2006, it was reported that Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Glomerulonephritis (MGN) were the commonest pr... [more]

Background: In 2006, it was reported that Focal and Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD) and Membranous Glomerulonephritis (MGN) were the commonest primary glomerular diseases identified from percutaneous kidney biopsies done in Jamaica for that year (n = 76). The sample size was thought to be small and might have affected the reported findings. So a three-year review of percutaneous kidney biopsies in Jamaica was carried out. Methods: Histology reports and clinical data were reviewed for percutaneous kidney biopsies performed from January 2005 to December 2007. Demographic data (age, gender), laboratory investigations such as serum urea, serum creatinine, proteinuria, haematuria, 24-hour urinary protein, and creatinine clearance, and clinical diagnosis were collected from the histology requisition form. Results: There was a total of 224 native kidney biopsies performed. There were 91 males (40.6%) and 133 females (59.4%). Age distribution showed a total number of 25 paediatric cases (11.2%) and 199 adult cases (88.8%). Proteinuria was present at 171 cases (76.3%) and haematuria in 86 cases (38.4%). Of the total biopsies done, 78 cases (39.2%) had primary glomerular diseases, 110 cases (55.3%) had secondary glomerular diseases and 11 (5.5%) biopsies were reported as either normal or inadequate for histological diagnosis. The most common reasons indicated for percutaneous kidney biopsy were proteinuria, haematuria and staging of lupus nephritis. Most common histological findings for primary glomerular disease after percutaneous kidney biopsy were FSGS (n = 34), MGN (n = 15) and MCD (n = 12). In secondary glomerular diseases (n = 110), there were more females (70.8%) than males. Systemic lupus erythematosus was present in 63.3%. Histology of lupus nephritis according to the International Society of Nephrologists classification shows Membranous Lupus Nephritis [MLN] (40.2%), Diffuse Lupus Nephritis [DLN] (19.5%) and Minimal Mesangial Lupus Nephritis [MMLN] (14.3%) as the common histological types. Conclusions: The most common histological finding for primary glomerular disease following percutaneous kidney biopsy was FSGS, MCD and MGN. Membranous Lupus Nephritis was the commonest histological type for lupus nephritis in this series.

Objectives: The purpose of the study was to determine the period prevalence of acute renal failure (ARF) after coronary bypass surgery (CABG) at the University Hospital of the Wes... [more]

Objectives: The purpose of the study was to determine the period prevalence of acute renal failure (ARF) after coronary bypass surgery (CABG) at the University Hospital of the West Iindies and to identify risk factors. Method: A retrospective analysis of patients who underwent CABG during the period 1994-2004 was done. Data collected included; age, gender weight, the presence of hypertension (HTN), diabetes mellitus (DM), hypercholesterolaemia, previous myocardial infarction (MI), bloodpressure on admission, urea and creatinine one year prior to surgery, on admission for surgery and post-surgery, duration of intra-operative hypotension, duration of cardiopulmonary bypass, perfusion pressure and the perioperative medications. Results: The case notes of 62 patients (68.9%) were obtainedfor analysis. There were 47 (75.8%) males and 15 females (24.2%) - a 3:1 ratio. The prevalence of HTN and DM in the study sample was 78% and 72% respectively, hypercholesterolaemia was 31% and a previous MI was 29%. There were no differences based on gender. Post CABG complications were: persistent postoperative hypotension (6.8%), congestive cardiac failure (CCF) (6.89,66), arrhythmia (6.8%), sepsis (6.8%), lower respiratory tract infection (LRTI) and pleural effusion (5.1%), heart block (3.4%), pulmonary embolism (1.7%), cellulitis and haematoma formation were 1.7%. Three patients had increases in postoperative creatinine values> 89 µmol/L over the postoperative value resulting in a prevalence of ARF of 5%. One of the three patients died and none received dialysis. There were no statistical difference inpre-operative clinical and biochemical characteristics based on the presence or absence of ARF. The presence of diabetes and increased length of stay were significant predictors of increasing postoperative creatinine values adjusting for pre-operative creatinine values. In addition, the presence of diabetes mellitus and male gender were significant predictors of increasing postoperative urea values. Conclusion: DM is a significant risk factor for the development of ARF post CABG.

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conduct... [more]

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conducted at six Jamaican healthcare facilities between July 1998 and December 1999 and included 605 patients with CRF. Men with CRF (57% of patients, mean age of 56.7 years) were significantly older than women (mean age 53.2 years). Hypertension was the most commonly associated medical condition (60.8% of patients) followed by diabetes mellitus (31.4% of patients). The estimated crude point prevalence of CRF in persons 20 years and over at the end of 1999 was 327 per million population. More than one-third of patients with CRF (39%) were receiving renal replacement therapy, the most common modality being haemodialysis, and only 1.8% of patients had received kidney transplantation. The prevalence of chronic renal failure was not increased in areas known to have high soil cadmium levels. Chronic renal failure is a significant public health problem in Jamaica and is placing an increasing financial burden on the healthcare sector.

Preterm labour remains a major obstetric problem with only poor methods for prediction of preterm birth and treatments of preterm labour with limited efficacy. Regulation of human... [more]

Preterm labour remains a major obstetric problem with only poor methods for prediction of preterm birth and treatments of preterm labour with limited efficacy. Regulation of human parturition is demonstrably different from that in most animals restricting opportunities for relevant research. Recent work suggests a placental clock mechanism regulating the length of pregnancy through the production of the placental peptide Corticotrophin Releasing Hormone. At the end of pregnancy most animals initiate labour with a fall in circulating progesterone concentrations but this does not happen in humans. In humans a functional progesterone withdrawal is initiated by a change in myometrial expression of progesterone receptors, specifically increase expression of the PRA isoforms, which is a dominant repressor of the activating receptor PRB. This new knowledge may help design better strategies for prediction and treatment of preterm labour.

OBJECTIVE: The purpose of this study was to examine the relationship of maternal serum activin A, inhibin A, and follistatin with fetal growth and placental function. STUDY DESIGN... [more]

OBJECTIVE: The purpose of this study was to examine the relationship of maternal serum activin A, inhibin A, and follistatin with fetal growth and placental function. STUDY DESIGN: Inhibin A, activin A, and follistatin were measured in maternal serum that was stored from normally grown (control subjects, n = 50) and small-for-gestational-age pregnancies (n = 49), prospectively classified as normal small-for-gestational-age pregnancy or fetal growth-restricted pregnancy with the use of umbilical artery Doppler ultrasound. RESULTS: Activin A and inhibin A were significantly increased in fetal growth-restricted pregnancies compared with control subjects (activin A: regression coefficient, 0.54, P < .001; inhibin A: regression coefficient, 0.47, P = .003). The activin:follistatin ratio was significantly higher in fetal growth-restricted pregnancies compared with control subjects (P < .001). There were no significant differences between analyte levels of normal small-for-gestational-age pregnancies and control subjects. CONCLUSION: Maternal serum activin A, inhibin A, and activin:follistatin ratio are raised in fetal growth-restricted pregnancies but not in normal small-for-gestational age pregnancies. This provides further evidence of the difference between subgroups within small-for-gestational-age pregnancies and emphasizes the need to stratify for this in research.

We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in ... [more]

We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feed-forward of fetal hypothalamic-pituitary-adrenal function, leading to birth.

In this study, local sewage sludge was acclimated to establish H2-producing enrichment cultures, which were used to convert sucrose to H2 with continuously stirred anaerobic biore... [more]

In this study, local sewage sludge was acclimated to establish H2-producing enrichment cultures, which were used to convert sucrose to H2 with continuously stirred anaerobic bioreactors. The steady-state behaviors of cell growth, substrate utilization, and product formation were closely monitored. Kinetic models were developed to describe and predict the experimental results from the H2-producing cultures. Operation at dilution rates (D) of 0.075-0.167 h-1 was preferable for H2 production, resulting in a H2 concentration of nearly 0.02 mol/l. The optimal hydrogen production rate was 0.105 mol/h occurring at D=0.125 h-1. The major volatile fatty acid produced was butyric acid (HBu), while acetic acid and propionic acid were also produced in lesser quantities. The major solvent product was ethanol, whose concentration was only 15% of that of HBu, indicating that the metabolic flow favors H2 production. The proposed model was able to interpret the trends of the experimental data. The maximum specific growth rate (µmax), Monod constant (Ks), and yield coefficient for cell growth (Yx/s) were estimated as 0.172 h-1, 68 mg COD/l, and 0.1 g/g, respectively. The model study also suggests that product formation in the continuous hydrogen-producing cultures was essentially a linear function of biomass concentration.

Although expression of liver fatty acid binding protein (L-FABP) modulates cell growth, it is not known if L-FABP also alters cell morphology and differentiation. Therefore, pluri... [more]

Although expression of liver fatty acid binding protein (L-FABP) modulates cell growth, it is not known if L-FABP also alters cell morphology and differentiation. Therefore, pluripotent embryonic stem cells were transfected with cDNA encoding L-FABP and a series of clones expressing increasing levels of L-FABP were isolated. Untransfected ES cells, as well as ES cells transfected only with empty vector, spontaneously differentiated from rounded adipocyte-like to fibroblast-like morphology, concomitant with marked reduction in expression of stage-specific embryonic antigen (SSEA-1). These changes in morphology and expression of SSEA-1 were greatest in ES cell clones expressing L-FABP above a threshold level. Immunofluorescence confocal microscopy revealed that L-FABP was primarily localized in a diffuse-cytosolic pattern along with a lesser degree of punctate L-FABP expression in the nucleus. Nuclear localization of L-FABP was preferentially increased in clones expressing higher levels of L-FABP. In summary, L-FABP expression altered ES cell morphology and expression of SSEA-1. Taken together with the fact that L-FABP was detected in the nucleus, these data suggested that L-FABP may play a more direct, heretofore unknown, role in regulating ES cell differentiation by acting in the nucleus as well as cytoplasm.

Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide that is expressed in the hypothalamus and the human placenta. Placental CRH production has been linked to th... [more]

Corticotrophin-releasing hormone (CRH) is a 41 amino acid neuropeptide that is expressed in the hypothalamus and the human placenta. Placental CRH production has been linked to the determination of gestational length in the human. Although encoded by a single copy gene, CRH expression in the placenta is regulated differently to the hypothalamus. Glucocorticoids stimulate CRH promoter activity in the placenta but inhibit it's activity in the hypothalamus, via mechanisms involving different regions of the CRH promoter. We discuss how various stimuli alter CRH promoter activity and why these responses are unique to the placenta.

Near the end of human pregnancy the concentration of placental corticotropin-releasing hormone in maternal blood rises exponentially. The rate of elevation of corticotropin-releas... [more]

Near the end of human pregnancy the concentration of placental corticotropin-releasing hormone in maternal blood rises exponentially. The rate of elevation of corticotropin-releasing hormone and its duration through time have been linked to the time of onset of labor. Paradoxically, although glucocorticoids are known to inhibit corticotropin-releasing hormone production within the hypothalamic-pituitary-adrenal axis, cortisol actually increases corticotropin-releasing hormone levels in several areas outside the hypothalamus, including the placenta. Placental corticotropin-releasing hormone may be an important component of a system that controls the normal maturation of the fetus and signals the initiation of labor. Abnormal elevations in corticotropin-releasing hormone, which may be a hormonal response to stressors arising in either the mother, placenta, or fetus, may prove to participate in the premature onset of parturition.

Transcranial Doppler ultrasonography was used to evaluate 2 patients who developed hyperperfusion syndromes after carotid endarterectomy. During the initial postoperative period, ... [more]

Transcranial Doppler ultrasonography was used to evaluate 2 patients who developed hyperperfusion syndromes after carotid endarterectomy. During the initial postoperative period, each patient had symptoms that were associated with elevated flow velocities in the ipsilateral cerebral vasculature. In addition, vascular resistance of these vessels was found to be abnormally low, as reflected by the Gosling pulsatility index. As the patients' symptoms improved, flow velocities decreased to normal levels and pulsatilities were noted to increase proportionately.

Management of patients harboring infectious intracranial aneurysms remains controversial because of the technical problems associated with the obliteration of these lesions as wel... [more]

Management of patients harboring infectious intracranial aneurysms remains controversial because of the technical problems associated with the obliteration of these lesions as well as their frequent regression during antibiotic therapy. A case of a ruptured bacterial aneurysm of the distal middle cerebral artery in which a segment of the artery was found to be inflamed and necrotic is presented. The ruptured portion of the sac was clipped, leaving a small tag of aneurysmal tissue. Five days later, this tag was found to have expanded into a second aneurysm. This second lesion resolved with antibiotic therapy. Because of the responsiveness of infected cerebral arteries to the appropriate antibiotics, a less than radical surgical tactic may be a successful alternative to excision of the diseases arterial segment followed by distal revascularization in treating these lesions.

Transcranial Doppler (TCD) evaluation of the intracranial vessels was performed in sixty-six patients, 51 of whom received conventional angiography either prior to or subsequent t... [more]

Transcranial Doppler (TCD) evaluation of the intracranial vessels was performed in sixty-six patients, 51 of whom received conventional angiography either prior to or subsequent to the ultrasonic arteriogram. Of the 14 patients evaluated for arteriovenous malformations (AVMs), TCD indicated the existence of the AVM in 10 cases. Of those 10 cases, 9 correlated with angiography. Twenty-one patients with aneurysms were evaluated with TCD and only 2 were detected. Twenty-three patients suspected of having ischemic disease were evaluated with TCD, which indicated the presence of stenosis in 21 patients. Twenty of those patients received conventional angiography, with 18 demonstrating significant stenosis.

Transcranial Doppler (TCD) ultrasonography was used to perform multiple examinations of 24 patients who sustained cranial injuries, 23 of whom progressed to death. In the 20 of th... [more]

Transcranial Doppler (TCD) ultrasonography was used to perform multiple examinations of 24 patients who sustained cranial injuries, 23 of whom progressed to death. In the 20 of these 23 patients for whom an adequate TCD signal could be obtained, a characteristic reverberating wave form pattern was observed, with an associated net flow velocity of < 10 cm/sec in all cases. In the last patient in our study group, a reverberating pattern was also identified, however, a net flow velocity of > 20 cm/sec was associated with functional recovery. Correlations of neurological function, TCD tracings, and net flow velocities permitted identification of characteristic hemodynamic changes that preceded cerebral circulatory arrest. Early changes included decreased flow velocity as well as an increase in pulse pressure. Late changes consisted of a persistent increase of pulse pressure with the appearance of retrograde flow velocities during diastole. In the end stage, complete diastolic retrograde flow velocities were found. These gave rise to the characteristic reverberating pattern mentioned earlier. Identification of flow velocity reversal alone, however, proved to be inadequate for making the diagnosis of brain death. Evaluation of net flow velocity (calculated at bedside) was found to be a more sensitive determinant of brain death and closely paralleled the patients' neurological function.

Transcranial Doppler (TCD) was used to assess collateral flow and to quantitate perfusion velocity changes in a group of 18 patients requiring temporary or permanent surgical occl... [more]

Transcranial Doppler (TCD) was used to assess collateral flow and to quantitate perfusion velocity changes in a group of 18 patients requiring temporary or permanent surgical occlusion of the internal carotid artery for treatment of their cerebrovascular lesions. Velocity measurements were correlated with times of occlusion and neurological outcome in order to assess safe vessel occlusion times and the need for an intraoperative shunt. These data were used to calculate a perfusion velocity index (PV(i)), which indicated that values > 2 were well tolerated, and values of < 1 were associated with ischemic signs. In addition, preoperative TCD examinations were combined with compressive maneuvers of the carotid artery in the neck to evaluate the feasibility of carotid clamp ligation for the treatment of giant intracranial aneurysms deemed unsuitable for direct clipping. When maintenance of neurological function and intracranial vessel flow velocities were found to be normal, with aneurysmal flow velocities of zero, ligation of the carotid artery could safely be undertaken. Finally, TCD allowed continuous surveillance of cerebral hemodynamics, which gave immediate assurance of postoperative ICA patency, as well as the ability to identify high velocity states associated with hyperperfusion syndromes, which occurred in two patients.

Patients treated with barbiturate coma for elevated intracranial pressure after head injury may suffer brain death. Since such patients have an iatrogenically induced absence of n... [more]

Patients treated with barbiturate coma for elevated intracranial pressure after head injury may suffer brain death. Since such patients have an iatrogenically induced absence of neurological function, brain death cannot be diagnosed clinically. Furthermore, as demonstrated by two of our patients, monitoring of intracranial pressure, even in the face of brain death, may show a low intracranial pressure and an intracranial pulse, suggesting the presence of adequate cerebral perfusion pressure and, therefore, brain viability. Under these circumstances, however, significant intracranial blood flow may be absent. Therefore, we suggest that a patient in barbiturate coma should undergo serial blood flow studies, even when the intracranial pressure is low and an intracranial pulse is present, to determine whether brain death has occurred.

Microvascular Doppler recordings were taken from the nidus and draining system of a dural spinal cord arteriovenous malformation during operative treatment. Doppler signals readil... [more]

Microvascular Doppler recordings were taken from the nidus and draining system of a dural spinal cord arteriovenous malformation during operative treatment. Doppler signals readily showed the direction of blood flow in the draining vein and the hemodynamic effects of surgical maneuvers. Recording during alterations of mean arterial blood pressure and partial carbon dioxide pressure (pCO2) demonstrated lack of autoregulation and impaired CO2 reactivity in the AVM nidus. Microvascular Doppler techniques provide useful intraoperative assessment of the hemodynamics of arteriovenous malformations of the spinal cord.

1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remain unclear. 2. We studied the relationship ... [more]

1. Endogenous opioids have been implicated in the control of breathing in neonates, but their role in ventilatory control in adults remain unclear. 2. We studied the relationship between circulating immunoreactive ß-endorphin and the ventilatory and mouth occlusion pressure responses to hypercapnia in 12 healthy male subjects. In addition, we examined the effect of repetitive hypercapnia on plasma ß-endorphin and cortisol levels. 3. A weak but significant negative relationship between the ventilatory response to hypercapnia and basal plasma ß-endorphin levels was observed (r = -0.35, P < 0.01). A similar negative relationship was noted between mouth occlusion pressure response to hypercapnia and basal plasma ß-endorphin levels (r = -0.36, P < 0.01). 4. Repetitive hypercapnia prevented the fall in plasma cortisol that occurred under control conditions (P < 0.02) but had no effect on plasma ß-endorphin. 5. We conclude that plasma ß-endorphin may play a role in the central chemical of breathing in man.

The met-enkephalin analogue, D-Ala2-MePhe4-met-enkephalin-(C)-ol (DAMME), was given i.v. to 6 normal subjects. Elevations in plasma prolactin and growth hormone (GH) occurred in association with significant falls in plasma epinephrine and norepinephrine. Dopamine rose 90 min after saline, but this was not seen after DAMME. Circulating melatonin and met-enkephalin levels failed to change. The data suggest that opiates may inhibit the release of plasma catecholamines, but do not alter endogenous levels of circulating met-enkephalin or elevate melatonin.

Research Collaborations

The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.

Having endured the grief of losing two children, former Wallabies player Dean Mumm and wife Sarah are linking with the Borne Foundation and Hunter Medical Research Institute (HMRI) to raise funds and awareness for research into premature birth.

Having endured the grief of losing two children, former Wallabies player Dean Mumm and wife Sarah are linking with the Borne Foundation and Hunter Medical Research Institute (HMRI) to raise funds and awareness for research into premature birth.